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C Young

Publications and source records attributed to C Young.

At least 235 records · Page 13Linked to original sources
PubMed1985

Genetic interactions of broad host-range plasmid RK2: evidence for a complex replication regulon.

The kil and kor genes of RK2 are novel genetic determinants further that the kil and kor network constitutes a replication regulon, and that perhaps the function of this regulon is to ensure expression of trfA at appropriate levels. The complexity of this regulon may reflect an ability of the system to adapt to the intracellular environments of a variety of hosts. Indeed, there is tantalizing evidence that regions encoding kil or kor genes are important to host range (1,2,6,28; Schmidhauser and Helinski, pers. comm.). We are therefore hopeful that the study of these genes and the eventual determination of the molecular basis of their actions will lead to a complete understanding of the replication control and broad host range capability of IncP plasmids.

Bacterial Proteins↗
PubMed1985

Canberra--the demographic experiment.

"The aims of this paper are to describe the demographic outcome of the early patterns of growth of...[Canberra, Australia], and to illustrate the way in which refinements in the measurement of demographic events can provide a more accurate picture of the true situation than occurs from crude measures. Much of the discussion is based on a comparison of the demographic situation in the ACT [Australian Capital Territory] with that in the nearest State capital city, Sydney, or with total Australia." Information is included on age structure, mobility, socioeconomic status, fertility, divorce, female labor force participation, and child care. "The ACT population has always been considered to be different from that of the other capital cities and from the overall population of Australia, and in many respects this is true. At the same time, however, recent data suggest that the ACT population profile is now converging towards the Australian experience."

Age Distribution↗
PubMed1985

korA function of promiscuous plasmid RK2: an autorepressor that inhibits expression of host-lethal gene kilA and replication gene trfA.

In broad host-range plasmid RK2, korA function prevents the lethal effect of kilA on Escherichia coli host cells and inhibits expression of trfA, the essential replication gene. From gene fusion and promoter replacement studies, we determined that control of kilA is also mediated at the level of gene expression and that the target resides in the kilA promoter region. The nucleotide sequence of this region shows the same two operator-like palindromes present in the previously sequenced promoters of trfA and korA. One of the palindromes (5'-GTTTAGCTAAAC-3') at the -10 position is sufficient to confer sensitivity to korA function. The presence of the same sequences in the korA promoter region suggested that korA might also regulate its own expression. Using the structural gene for chloramphenicol acetyltransferase (cat) fused to the korA promoter, we found that korA gene expression is indeed autoregulated. The results show that korA gene product is very likely a repressor that negatively regulates expression of at least three different genes by interacting with an operator-like sequence in their promoter regions. Coordinate regulation of host-lethal gene kilA and essential replication gene trfA by a common mechanism also supports our hypothesis that these genes are functionally related.

Bacterial Proteins↗
PubMed1985

Repatterning of stroke rehabilitation clients following return to life in the community.

The purpose of this study was to learn more about problems stroke patients experience after rehabilitation and how they perceive and interact with their environment. Findings indicate that nurses need to consider individual life patterns, current goals and the resources and impediments of the home and community environment in planning interventions. Subjects wanted a challenging but not overly stressful environment. Most of their energy was consumed with accomplishing the activities of daily living. Complex planning and timing were necessary to continue a few pleasurable activities. Advocates are needed for better design and accessibility in the environment of our aging population, with increasing numbers of chronically ill and disabled, and for all people.

Activities of Daily Living↗
PubMed1985

Replication control in promiscuous plasmid RK2: kil and kor functions affect expression of the essential replication gene trfA.

We previously reported that broad-host-range plasmid RK2 encodes multiple host-lethal kil determinants (kilA, kilB1, kilB2, and kilC) which are controlled by RK2-specified kor functions (korA, korB, and korC). Here we show that kil and kor determinants have significant effects on RK2 replication control. First, korA and korB inhibit the replication of certain RK2 derivatives, unless plasmid replication is made independent of the essential RK2 gene trfA. Second, kilB1 exerts a strong effect on this interaction. If the target plasmid is defective in kilB1, sensitivity to korA and korB is enhanced at least 100-fold. Thus, korA and korB act negatively on RK2 replication, whereas kilB1 acts in a positive manner to counteract this effect. A mutant RK2 derivative, resistant to korA and korB, was found to have fused a new promoter to trfA, indicating that the targets for korA and korB are at the 5' end of the trfA gene. We constructed a trfA-lacZ fusion and found that synthesis of beta-galactosidase is inhibited by korA and korB. Thus korA, korB, and kilB1 influence RK2 replication by regulating trfA expression. We conclude that the network of kil and kor determinants is part of a replication control system for RK2.

Bacterial Proteins↗
PubMed1985

Metoclopramide: dose-related toxicity and preliminary antiemetic studies in children receiving cancer chemotherapy.

Prior studies in adults have shown that metoclopramide (MCP), when given in high intravenous (IV) doses (2 mg/kg), is a highly effective antiemetic for chemotherapy-induced vomiting. It is well-tolerated in older adults, but younger adults have an increased disposition to acute extrapyramidal reactions (EPRs). Before studying the efficacy of MCP as an antiemetic in children, we first had to establish the safe dose range. We performed a dose-increase MCP toxicity study in children receiving highly emetic chemotherapy such as cisplatin (120 mg/m2) or cyclophosphamide (greater than 900 mg/m2), beginning with a dose of 0.2 mg/kg and increasing the dose in nine steps to 3 mg/kg. MCP was given every two hours for four doses beginning one-half hour before chemotherapy. To reduce the incidence of EPRs, we added concomitant diphenhydramine. In MCP doses less than 2 mg, toxicity was minimal. In doses greater than or equal to 2 mg, 4/27 (15%) had EPRs and 9/27 (33%) had akathisia. Children who received two consecutive days of MCP had a higher frequency of EPRs. Metoclopramide (2 mg/kg) had promising antiemetic efficacy in a preliminary nonrandomized trial. Chemotherapy-experienced children vomited fewer than five times in 9/21 (43%) trials, and new patients vomited fewer than five times in 7/10 (70%) trials. MCP will become more useful as an antiemetic in children if better measures to prevent EPRs can be developed. Chemotherapy-induced emesis has the same negative implications in children as it does in adults and optimum antiemetic regimens can only be discovered by conducting randomized clinical trials in children.

Adolescent↗
PubMed1985

Phase I evaluation and pharmacokinetic study of weekly iv thymidine and 5-FU in patients with advanced colorectal carcinoma.

A phase I study of weekly iv thymidine (TdR) and 5-FU was carried out in patients with advanced colorectal carcinoma using two dosage schedules. Schedule 1 employed a 3-hour infusion of TdR (6-8 g/m2/hour) followed immediately by a bolus of 5-FU (100-200 mg/m2). Schedule 2 used a slightly larger dose of TdR (18 g/m2/hour for 1.5 hours), with 5-FU given 30 minutes after the TdR infusion was started. Myelosuppression was observed erratically at the higher doses of 5-FU. Diarrhea and severe fatigue were seen frequently with Schedule 1. CNS side effects were the dose-limiting effects for both schedules. For long-term use the maximally tolerated 5-FU doses were 100 mg/m2/week for Schedule 1 and 175 mg/m2/week for Schedule 2. In pharmacokinetic studies in five patients, both schedules produced prolonged plasma beta-half-lives of 5-FU (96-189 minutes). Extensive formation of floxuridine was seen with both schedules. It appears likely that CNS toxic effects are characteristic of TdR-containing 5-FU regimens and would limit the therapeutic potential of this approach.

Adult↗
PubMed1984

Coli surface antigens 1 and 3 of colonization factor antigen II-positive enterotoxigenic Escherichia coli: morphology, purification, and immune responses in humans.

Enterotoxigenic Escherichia coli (ETEC) of serotype O6:H16, biotype A, bearing colonization factor antigen II (CFA/II) possesses two distinct coli surface antigens, CS1 and CS3, whereas CFA/II-positive ETEC of serotype O8:H9 manifests only CS3. CS1 has been shown to be fimbrial in nature, but heretofore the morphology of CS3 has not been described. Accordingly, by immune electron microscopy we investigated the morphological characteristics of CS3 on bacterial cells and after purification. CS3 was found to consist of thin (2-nm), flexible, wiry, "fibrillar" fimbriae, visible both on bacteria (O6:H16, biotype A, and O8:H9 strains) and in the pure state. In contrast, CS1 exists as wider (6-nm), rigid fimbriae on the surface of O6:H16, biotype A, strains. By the use of antisera to CS1 and CS3 in immune electron microscopy, immunodiffusion in gel, and immunoblotting techniques, CS1 and CS3 were found to be immunologically as well as morphologically distinct. Six of nine volunteers who developed diarrhea after challenge with an O139:H28 ETEC strain bearing CS1 and CS3 had significant serological rises to purified CS1 and CS3 antigens, suggesting that both antigens are elaborated in vivo, play a role in pathogenesis, and stimulate an immune response.

Antibody Formation↗
PubMed1984

Evaluation of the human immune response to outer membrane proteins of Vibrio cholerae.

The immune response of 114 volunteers with diarrhea after experimental challenge with four strains of Vibrio cholerae O1 was characterized in a microtiter enzyme-linked immunosorbent assay antibody detection system by using a partially purified outer membrane preparation (OMP) from these strains as an antigen. Analysis of paired sera from 29 persons with noncholera diarrhea (negative control population), demonstrated that a rise in net optical density greater than 0.10 was significant. A total of 50% of the 79 cholera volunteers challenged with El Tor biotype and 54% of the 35 volunteers challenged with classical biotype had significant rises in immunoglobulin G anti-OMP. Paired sera that showed significant rises when tested against homologous OMP all manifested significant rises when also tested against a serotype-heterologous OMP. Immunoblotting techniques showed that the antigens to which antibodies were reacting were mainly protein in nature, not lipopolysaccharide. Furthermore, absorption with lipopolysaccharide decreased the optical density by a mean of only 12% (0 to 30%), corroborating that antibody was mainly directed against OMP and not lipopolysaccharide. This study indicates that there is a human immunoglobulin G response to OMP during clinical cholera infection and that this response is constant among bio- and serotypes.

Antibody Formation↗
PubMed1984

Gene regulation in plasmid RK2: positive control by korA in the expression of korC.

The broad-host-range plasmid RK2 encodes three host-lethal kil genes whose actions are controlled by specific kor genes. We have shown previously that the 0' to 5.5' region of RK2 encodes both kilA and korC. Because of the lethal effect of kilA, plasmids with this region cannot be maintained in Escherichia coli unless the RK2 korA gene is also present. To investigate korC in the absence of kilA and therefore of korA, we first mapped kilA and korC to specific segments of the cloned 0' to 5.5' region. This allowed us to construct a korC+ plasmid missing the kilA region and thereby removed the need to have korA in the cell. We found that this korC-encoding plasmid alone is insufficient to control kilC. The korA function is required, and it can be supplied in trans. We also constructed a kilA+ korC- plasmid and found that korA is sufficient to control kilA. Thus, in addition to acting negatively to control kilA, korA acts positively to allow korC control of kilC. This korA dependence of korC is bypassed in a rho-115 mutant of E. coli. We consider the possibility that korA product acts as an antiterminator of transcription in korC expression.

Chromosome Mapping↗
PubMed1983

The genetic analysis of adenovirus recombination in triparental and superinfection crosses.

Previous genetic and molecular data suggest that adenovirus genomes can undergo several rounds of recombination before being encapsidated (C. S. H. Young and S. J. Silverstein, Virology 101, 503-515). Two predictions of this hypothesis have been tested. The first is that infection with three differentially marked parental viruses should lead to the appearance of recombinants with genetic contributions from all three parents. In a triparental cross, involving two strains with different ts mutations in chimeric Ad5/Ad2+ND1 backgrounds, and a third strain containing both ts mutations in an Ad5 background, it was demonstrated that multiple recombinations, involving distinguishable restriction endonuclease sites and host range markers from all three parents, were common. The second prediction, from previous kinetic data, is that cells are recombinationally proficient from the eclipse period well into the exponential rise period. This has been tested by superinfecting singly infected cultures, both during eclipse and in early exponential phase. Recombinant viruses were produced in these superinfections, demonstrating that the early to late switch in the replicative cycle does not inhibit recombination. From the temporal appearance of recombinants moreover, it seems likely that recombination functions, and the DNA structures necessary to initiate recombination, are present well into the late phase of replication.

Adenoviruses, Human↗
PubMed1983

Voluntary regionalization and associated trends in perinatal care: the Nova Scotia Reproductive Care Program.

The Nova Scotia Reproductive Care Program is a system of voluntary regionalization that involves the 37 hospitals in the province that provide obstetric care to a population of 850,000. Between 1971 and 1980, the perinatal mortality rate in the central tertiary care unit for nonreferred patients fell progressively from 12.5 per 1,000 total births to 5.16. For all cases, including high-risk referrals, this rate has fallen from 12.7 to 7.2. During the same interval, the perinatal mortality rate for the province's seven regional hospitals fell from 18.7 to 12.2, and that for the 28 community hospitals fell from 18.4 to 7.0. Analysis of these reductions by fitted trend lines demonstrates statistical significance. Further analysis demonstrates that, with regionalization of perinatal services, it is possible to reduce the perinatal mortality rate in small community hospitals to levels that approximate those of a sophisticated tertiary care hospital.

Female↗
PubMed1983

Effects of fat level, feeding period, and source of fat on lipid fluidity and physical state of rabbit plasma lipoproteins.

Elevating fat content from 5 to 20% of diet by weight or extending the feeding period from 6 months to more than 1 year did not substantially alter the fluidity of rabbit plasma lipoprotein lipid domains. Dietary fatty acid saturation was not adequate as a predictor of lipoprotein fluidity. Rabbits fed corn oil, high in polyunsaturated fatty acid content, did not have more fluid lipoproteins than rabbits fed cocoa butter which contains a high level of saturated long chain fatty acids. Order parameters calculated from fluorescence depolarization measurements with diphenylhexatriene (DPH) showed that very low density lipoprotein (VLDL) lipids were in highly fluid or 'liquid' states at or below body temperature. Order parameter data showed transitions from ordered phase to isotropic liquid in low density lipoproteins (LDL) that were heretofore unnoted with DPH fluorescence depolarization measurements. The transition temperature was inversely related to the LDL triglyceride content, indicating probe intercalation between the fatty acyl chains of the core triacylglycerols in VLDL and LDL.

Animals↗